Taste transduction is one of the most sophisticated forms of chemotransduction in animals. Gustatory signaling is found throughout the animal kingdom, from simple metazoans to the most complex vertebrates. Its main purpose is to provide a reliable signaling response to non-volatile ligands. Humans typically distinguish several perceptual taste qualities or modalities: sweet, sour, salty, bitter and umami. Each of these modalities is thought to be mediated by distinct signaling pathways mediated by receptors or channels, leading to receptor cell depolarization, generation of a receptor or action potential, and release of neurotransmitter at gustatory afferent neuron synapses.
Taste transduction in animals is mediated by specialized neuroepithelial cells, referred to as taste receptor cells. These cells are organized into groups of about 40 to 100 cells to form taste buds. Taste buds contain precursor cells, support cells, and taste receptor cells. Receptor cells are innervated at their base by afferent nerve endings that transmit information to the taste centers of the cortex through synapses in the brain stem and thalamus. Taste buds are distributed into different papillae in the tongue epithelium. Circumvallate papillae, found at the very back of the tongue, contain hundreds to thousands of taste buds. By contrast, foliate papillae, localized to the posterior lateral edge of the tongue, contain dozens to hundreds of taste buds. Further, fungiform papillae, located on the anterior two-thirds of the tongue, contain only a single or few taste buds, depending upon the species. Taste cells are also found in the palate and other tissues, such as the esophagus and the stomach.
Taste buds are ovoid structures and are primarily embedded within the epithelium of the tongue. It is believed that taste transduction is initiated at the apical portion of a taste bud at the taste pore, where microvilli of the taste receptor cells make contact with the outside environment. Various taste stimulants cause either depolarization (i.e., a reduction in membrane potential) or hyperpolarization (i.e., an increase in membrane potential) of taste cells and regulate neurotransmitter release from the cells at chemical synapses with afferent nerve fibers. The primary gustatory sensory fibers, which receive the chemical signals from the sensory cells, enter the base of each taste bud. Inter-cellular connections between taste cells in the same bud may also modulate the signals transmitted to the afferent nerve fibers. Molecules that elicit specific taste sensations are often referred to as “tastants.” Although much is known about the psychophysics and physiology of taste cell function, very little is known about the molecules and pathways that mediate its sensory signaling response.
In general, each taste modality is associated with particular types of receptor proteins expressed in some of the cells that form each taste bud. Genes encoding taste receptor proteins for sweet, bitter, umami and salty taste substances have been cloned from a variety of species, including humans. The nature of the coupling of stimulus-receptor interaction to a cellular response in the receptor cells has also been defined for some receptors. Some of these receptors have been used to develop bioassays for use in identifying potential taste enhancers, blockers and modifiers. Although these “chip” based systems have the potential for high throughput screening of large numbers of compounds, they do not incorporate the normal cellular components of the taste signaling pathways that are required for normal receptor-response coupling. Consequently, these assays are best at providing initial information about binding of potential stimuli with a particular receptor. They do not, however, provide information about a subsequent cellular response, if any, to the test substance.
An alternative approach is to express cloned taste receptors in heterologous cells, typically a mammalian cell line such as human embryonic kidney cells (HEK293), and to measure changes in intracellular calcium induced by taste stimuli. This approach requires coupling between stimulus-receptor interaction and a cellular pathway leading to an increase in calcium, and it permits measurements in many cells at once. The normal cellular organization of the taste receptor unit, the taste bud, however, is lost along with any processing of taste information occurring between cells within the taste bud. This limitation is particularly important in light of recent results suggesting that sweet and bitter receptors are localized in taste cells that do not directly communicate with afferent nerve fibers, but rather communicate with adjacent taste bud cells that are innervated.